A Primary Spinal Nongerminomatous Germ Cell Tumor With Multiple Intracranial Metastases in a Toddler.

Central nervous system germ cell tumors (CNS-GCTs) comprise 4% of all pediatric CNS tumors, with one third being nongerminomatous GCT (CNS-NG-GCT) type. The majority of these tumors arise in the intracranial compartment with 20% having drop metastases in the spine. We present a rare case of a 2-year-old boy with a primary intradural-extramedullary NG-GCT arising from the lumbosacral spine with a trifecta of unfavorable features, that is, young age, alpha-feto protein >1000 ng/mL, and disseminated disease within the cranium. Owing to his young age, he was treated with chemotherapy alone, avoiding radiation. His tumor marker (alpha-feto protein) declined from 8468 to 10 k-U/L over 8 weeks, and he remained in remission at the last follow-up. This atypical presentation of an intradural-extramedullary tumor with cranial dissemination in a childhood NG-GCT has yet to be described in the literature. Here we use this opportunity to highlight the treatment strategies and challenges in this unique clinical case.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

A Novel Case of Homozygous Interferon Alpha/Beta Receptor Alpha Chain (IFNAR1) Deficiency With Hemophagocytic Lymphohistiocytosis.

We present a case of complete deficiency of the interferon alpha/beta receptor alpha chain (IFNAR1) in a child with fatal systemic hyperinflammation, apparently provoked by live-attenuated viral vaccination. Such pathologic hyperinflammation, fulfilling criteria for hemophagocytic lymphohistiocytosis, is an emerging phenotype accompanying inborn errors of type I interferon immunity.

Metabolite selection for machine learning in childhood brain tumour classification.

MRS can provide high accuracy in the diagnosis of childhood brain tumours when combined with machine learning. A feature selection method such as principal component analysis is commonly used to reduce the dimensionality of metabolite profiles prior to classification. However, an alternative approach of identifying the optimal set of metabolites has not been fully evaluated, possibly due to the challenges of defining this for a multi-class problem. This study aims to investigate metabolite selection from in vivo MRS for childhood brain tumour classification. Multi-site 1.5 T and 3 T cohorts of patients with a brain tumour and histological diagnosis of ependymoma, medulloblastoma and pilocytic astrocytoma were retrospectively evaluated. Dimensionality reduction was undertaken by selecting metabolite concentrations through multi-class receiver operating characteristics and compared with principal component analysis. Classification accuracy was determined through leave-one-out and k-fold cross-validation. Metabolites identified as crucial in tumour classification include myo-inositol (P < 0.05, AUC=0.81±0.01 ), total lipids and macromolecules at 0.9 ppm (P < 0.05, AUC=0.78±0.01 ) and total creatine (P < 0.05, AUC=0.77±0.01 ) for the 1.5 T cohort, and glycine (P < 0.05, AUC=0.79±0.01 ), total N-acetylaspartate (P < 0.05, AUC=0.79±0.01 ) and total choline (P < 0.05, AUC=0.75±0.01 ) for the 3 T cohort. Compared with the principal components, the selected metabolites were able to provide significantly improved discrimination between the tumours through most classifiers (P < 0.05). The highest balanced classification accuracy determined through leave-one-out cross-validation was 85% for 1.5 T 1 H-MRS through support vector machine and 75% for 3 T 1 H-MRS through linear discriminant analysis after oversampling the minority. The study suggests that a group of crucial metabolites helps to achieve better discrimination between childhood brain tumours.

Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.

BACKGROUND: Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. OBJECTIVE: We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types. RESULTS: Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K2=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference. CONCLUSION: Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.

Ground Target Tracking Using an Airborne Angle-Only Sensor with Terrain Uncertainty and Sensor Biases.

Airborne angle-only sensors can be used to track stationary or mobile ground targets. In order to make the problem observable in 3-dimensions (3-D), the height of the target (i.e., the height of the terrain) from the sea-level is needed to be known. In most of the existing works, the terrain height is assumed to be known accurately. However, the terrain height is usually obtained from Digital Terrain Elevation Data (DTED), which has different resolution levels. Ignoring the terrain height uncertainty in a tracking algorithm will lead to a bias in the estimated states. In addition to the terrain uncertainty, another common source of uncertainty in angle-only sensors is the sensor biases. Both these uncertainties must be handled properly to obtain better tracking accuracy. In this paper, we propose algorithms to estimate the sensor biases with the target(s) of opportunity and algorithms to track targets with terrain and sensor bias uncertainties. Sensor bias uncertainties can be reduced by estimating the biases using the measurements from the target(s) of opportunity with known horizontal positions. This step can be an optional step in an angle-only tracking problem. In this work, we have proposed algorithms to pick optimal targets of opportunity to obtain better bias estimation and algorithms to estimate the biases with the selected target(s) of opportunity. Finally, we provide a filtering framework to track the targets with terrain and bias uncertainties. The Posterior Cramer-Rao Lower Bound (PCRLB), which provides the lower bound on achievable estimation error, is derived for the single target filtering with an angle-only sensor with terrain uncertainty and measurement biases. The effectiveness of the proposed algorithms is verified by Monte Carlo simulations. The simulation results show that sensor biases can be estimated accurately using the target(s) of opportunity and the tracking accuracies of the targets can be improved significantly using the proposed algorithms when the terrain and bias uncertainties are present.

Unusual cause of treatable Parkinsonism.

A 78-year-old woman presented with features of bilateral, asymmetric Parkinsonism for 1 year, with prominent difficulties with continence, swallowing and apathy. Brain imaging showed evidence of chronic venous sinus thrombosis with dilated serpiginous vessels over the brain surface in keeping with a dural arteriovenous fistula, together with high T2 signal on MRI in the basal ganglia. Having responded only modestly to levodopa, she received 6 months of anticoagulation followed by embolisation of the dural arteriovenous fistula, with good response. Cerebral dural arteriovenous fistula is a rare, structural cause of atypical Parkinsonism.

Application of pattern recognition techniques for classification of pediatric brain tumors by in vivo 3T 1 H-MR spectroscopy-A multi-center study.

PURPOSE: 3T magnetic resonance scanners have boosted clinical application of 1 H-MR spectroscopy (MRS) by offering an improved signal-to-noise ratio and increased spectral resolution, thereby identifying more metabolites and extending the range of metabolic information. Spectroscopic data from clinical 1.5T MR scanners has been shown to discriminate between pediatric brain tumors by applying machine learning techniques to further aid diagnosis. The purpose of this multi-center study was to investigate the discriminative potential of metabolite profiles obtained from 3T scanners in classifying pediatric brain tumors. METHODS: A total of 41 pediatric patients with brain tumors (17 medulloblastomas, 20 pilocytic astrocytomas, and 4 ependymomas) were scanned across four different hospitals. Raw spectroscopy data were processed using TARQUIN. Borderline synthetic minority oversampling technique was used to correct for the data skewness. Different classifiers were trained using linear discriminative analysis, support vector machine, and random forest techniques. RESULTS: Support vector machine had the highest balanced accuracy for discriminating the three tumor types. The balanced accuracy achieved was higher than the balanced accuracy previously reported for similar multi-center dataset from 1.5T magnets with echo time 20 to 32 ms alone. CONCLUSION: This study showed that 3T MRS can detect key differences in metabolite profiles for the main types of childhood tumors. Magn Reson Med 79:2359-2366, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Feasibility trial of an early therapy in perinatal stroke (eTIPS).

BACKGROUND: Perinatal stroke (PS) affects up to 1/2300 infants and frequently leads to unilateral cerebral palsy (UCP). Preterm-born infants affected by unilateral haemorrhagic parenchymal infarction (HPI) are also at risk of UCP. To date no standardised early therapy approach exists, yet early intervention could be highly effective, by positively influencing processes of activity-dependent plasticity within the developing nervous system including the corticospinal tract. Our aim was to test feasibility and acceptability of an "early Therapy In Perinatal Stroke" (eTIPS) intervention, aiming ultimately to improve motor outcome. METHODS: Design: Feasibility trial, North-East England, August 2015-September 2017. Participants were infants with PS or HPI, their carers and therapists. The intervention consisted of a parent-delivered lateralised therapy approach starting from term equivalent age and continuing until 6 months corrected age. The outcome measures were feasibility (recruitment and retention rates) and acceptability of the intervention (parental questionnaires including the Warwick-Edinburgh Mental Wellbeing Scale (WEBWMS), qualitative observations and in-depth interviews with parents and therapists). We also reviewed clinical imaging data and undertook assessments of motor function, including the Hand Assessment for Infants (HAI). Assessments were also piloted in typically developing (TD) infants, to provide further information on their ease of use and acceptability. RESULTS: Over a period of 18 months we screened 20 infants referred as PS/HPI: 14 met the inclusion criteria and 13 took part. At 6 months, 11 (85%) of those enrolled had completed the final assessment. Parents valued the intervention and found it acceptable and workable. There were no adverse events related to the intervention. We recruited 14 TD infants, one of whom died prior to undertaking any assessments and one of whom was subsequently found to have a condition affecting neurodevelopmental progress: thus, data for 12 TD infants was analysed to 6 months. The HAI was well tolerated by infants and highly valued by parents. Completion rates for the WEBWMS were high and did not suggest any adverse effect of engagement in eTIPS on parental mental wellbeing. CONCLUSION: The eTIPS intervention was feasible to deliver and acceptable to families. We plan to investigate efficacy in a multicentre randomised controlled trial. TRIAL REGISTRATION: ISRCTN12547427 (registration request submitted 28/05/2015; retrospectively registered, 30/09/2015).

SIOP PODC Adapted treatment guidelines for low grade gliomas in low and middle income settings.

Effective treatment of children with low grade glioma (LGG) requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition, the treating centre should have the capacity to manage a variety of LGG and treatment-associated complications. These requirements have made it difficult for many centers in low and middle-income countries (LMIC) to offer effective treatment and follow up. This article provides management recommendations for children with LGG according to the level of facilities available.

SIOP PODC adapted treatment recommendations for standard-risk medulloblastoma in low and middle income settings.

Effective treatment of children with medulloblastoma requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition the treating centre should have the capacity to effectively screen and manage any tumour and treatment-associated complications. These requirements have made it difficult for many low and middle-income countries (LMIC) centres to offer curative treatment. This article provides management recommendations for children with standard-risk medulloblastoma (localised tumours in children over the age of 3-5 years) according to the level of facilities available.

Broadening the Spectrum of SLC22A5 Phenotype: Primary Carnitine Deficiency Presenting with Focal Myoclonus.

Primary carnitine deficiency (PCD) is caused by pathogenic variants of the SLC22A5 gene, which encodes a transmembrane protein that functions as a high affinity carnitine transporter. Carnitine is essential for the transport of acyl-CoA, produced from fatty acids, into the mitochondria where they are oxidised to produce energy. We present the case history of an 8-year-old boy who presented with fever, lethargy, focal rhythmic (3 Hz) left wrist twitching, and severe encephalopathy. MRI brain showed basal ganglia involvement. Metabolic investigations revealed low serum carnitine; whole genome sequencing confirmed compound heterozygous SLC22A5 mutations. With carnitine replacement, intensive care support, and neurorehabilitation, he made a remarkable recovery, regaining independent breathing, speech, mobility, and hand use. Seizure presentation in PCD is rare and presentation with sustained focal myoclonus has not been previously reported. This case expands the known phenotype of PCD. Prompt carnitine replacement is imperative.

A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke.

The aim of this prospective observational longitudinal study was to explore and decipher the predictive value of prospective MRI biomarkers in the brain and lower limb muscles for 3-month lower limb motor recovery following stroke. In the brain, we measured the integrity of the corticospinal tract (fractional anisotropy/"FA"). In the muscles, we measured volume, fatty replacement (fat fraction analysis and proton spectroscopy) and oedema. Measurements were taken at two time points: (1) within 4 weeks of stroke (baseline measurement, clinical and imaging) and (2) 3 months following stroke (follow up measurement, clinical only). Clinical measurements consisted of assessments of functional ability and strength (Fugl-Meyer score, motor NIHSS, Functional Ambulation Category/"FAC", and muscle dynamometry). Twenty-three patients completed imaging and clinical assessments at baseline and follow-up; five patients had partial imaging assessment. The results provided some evidence that damage to the corticospinal tract would result in less motor recovery: recovery of the Fugl-Meyer score and dynamometric ankle plantarflexion, ankle dorsiflexion, and knee extension correlated positively and significantly with fractional anisotropy (0.406-0.457; p = 0.034-p = 0.016). However, fractional anisotropy demonstrated a negative correlation with recovery of the Functional Ambulation Category (-0.359, p = 0.046). For the muscle imaging, significant inverse correlation was observed between vastus lateralis fat fraction vs. NIHSS recovery (-0.401, p = 0.04), and a strong positive correlation was observed between ratio of intra- to extra-myocellular lipid concentrations and the recovery of knee flexion (0.709, p = 0.007). This study supports previous literature indicating a positive correlation between the integrity of the corticospinal tract and motor recovery post-stroke, expanding the limited available literature describing this relationship specifically for the lower limb. However, recovery of functional ambulation behaved differently to other clinical recovery markers by demonstrating an inverse relationship with corticospinal tract integrity. The study also introduces some muscle imaging biomarkers as potentially valuable in the prediction of 3-month lower limb motor recovery following stroke.

Applying machine learning classifiers to automate quality assessment of paediatric dynamic susceptibility contrast (DSC-) MRI data.

OBJECTIVE: Investigate the performance of qualitative review (QR) for assessing dynamic susceptibility contrast (DSC-) MRI data quality in paediatric normal brain and develop an automated alternative to QR. METHODS: 1027 signal-time courses were assessed by Reviewer 1 using QR. 243 were additionally assessed by Reviewer 2 and % disagreements and Cohen's κ (κ) were calculated. The signal drop-to-noise ratio (SDNR), root mean square error (RMSE), full width half maximum (FWHM) and percentage signal recovery (PSR) were calculated for the 1027 signal-time courses. Data quality thresholds for each measure were determined using QR results. The measures and QR results trained machine learning classifiers. Sensitivity, specificity, precision, classification error and area under the curve from a receiver operating characteristic curve were calculated for each threshold and classifier. RESULTS: Comparing reviewers gave 7% disagreements and κ = 0.83. Data quality thresholds of: 7.6 for SDNR; 0.019 for RMSE; 3 s and 19 s for FWHM; and 42.9 and 130.4% for PSR were produced. SDNR gave the best sensitivity, specificity, precision, classification error and area under the curve values of 0.86, 0.86, 0.93, 14.2% and 0.83. Random forest was the best machine learning classifier, giving sensitivity, specificity, precision, classification error and area under the curve of 0.94, 0.83, 0.93, 9.3% and 0.89. CONCLUSION: The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification. ADVANCES IN KNOWLEDGE: A new automated quality control method was developed, which trained machine learning classifiers using QR results.

Atypical findings in three patients with Pai syndrome and literature review.

Pai syndrome is a rare disorder characterized by congenital nasal or facial polyp, midline cleft lip, pericallosal lipoma, ocular anomalies, and normal neuropsychological development. Here, we report on three patients with Pai syndrome and atypical findings: temporal triangular alopecia, posterior lenticonus, bilateral palatal pits, bifid uvula, hypospadias, sacral dimple, true tracheal bronchus, and epilepsy. Thirty-three cases of Pai syndrome have been described so far. We present a review of the previously reported cases and suggest modified diagnostic criteria for Pai syndrome.

The importance of biopsy following radiological diagnosis of relapsed medulloblastoma.

We report the case of a 13-year old with a radiological diagnosis of relapsed medulloblastoma. Eighteen months after the last course of palliative chemotherapy MRI showed radiological resolution. The lesions were retrospectively assumed to be a radiation effect, highlighting the potential benefits of biopsy to confirm presumed radiological recurrence.

Settling moths are the vital component of pollination in Himalayan ecosystem of North-East India, pollen transfer network approach revealed.

Majority of the pollination related studies are based on the diurnal pollinators, and the nocturnal pollinators received less scientific attention. We reveal the significance of settling moths in pollination of angiosperm families in Himalayan ecosystem of North-East India. The refined and novel method of pollen extraction from the proboscides provides a more robust assessment of the pollen carrying capacity. The study is based on one of the largest data sets (140 pollen transporter moth species (PTMS)), with interpretation based on seasonal as well as altitudinal data. In the present study about 65% moths (91 species) carried sufficient quantities of pollen grains to be considered as potential pollinators (PPMS). Teliphasa sp. (Crambidae) and Cuculia sp. (Noctuidae) are found to carry the highest quantity of pollen. We found pollen grains of 21 plant families and the abundant pollen are from Betulaceae, Fabaceae, Rosaceae and Ericaceae. Species composition of PTMS and PPMS in pre-monsoon, monsoon, and post-monsoon revealed the dominance of Geometridae. Maximum diversity of PTMS and PPMS is found from 2000 to 2500 m altitude. The nocturnal pollen transfer network matrices exhibited high degree of selectivity (H2' = 0.86).

Accelerated myelination with motor system involvement in a neonate with immediate postnatal onset of seizures and hemimegalencephaly.

The timetable for normal myelination in the developing brain on MRI is well described. Beyond the genetically determined myelination process, environmental or other incidental factors may modulate the actual myelination, globally or regionally. Delayed myelination is well known in many pathological conditions interfering with adequate energy or myelin precursor supply. Rare but specific conditions where the normal process of myelination is accelerated are also known. We describe a case of early postnatal epilepsy demonstrating a striking degree of accelerated myelination both in the cerebral tissue adjacent to the presumed epileptic focus and along the ipsilateral pyramidal tract through the brainstem, a feature not previously described in the literature. This distal myelination highlights the peculiar system involvement pattern of function-induced myelination rather than simply regional myelination in response to an epileptic or other stimulus. This may have implications on our understanding of the development of function systems (visual, auditory, motor, sensory, etc.) or even the more complex interactive process of learning and may open new therapeutic opportunities in pathological functional conditions previously believed to be incurable.

Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies.

White matter changes have been investigated in Alzheimer's disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson's Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex.

Case report: MRI findings of acute uremic encephalopathy in a 1-year-old boy.

We present a 1-year-old boy who presented to the emergency department with a 7-day history of diarrhoea and vomiting. The initial renal function profile demonstrated a urea of 55 mmol l-1 (normal range between 5 and 20 mmol l-1), creatinine 695 micromol/L (normal range between 62-106 micromol/L) and potassium 9.1 mmol l-1 (normal range between 3.5-5.0 mmol l-1), with a profound metabolic acidosis. Upon examination, there were no significant findings, specifically no neurological abnormality. He was prescribed back-to-back Salbutamol nebulisers, to increase the shift of extracellular potassium into the intracellular space, followed by i.v. calcium gluconate, with some improvement in potassium levels. A further 5 mmol of sodium bicarbonate was given, as well as a stat dose of 1 mg/kg furosemide, and per rectal calcium resonium. He was then commenced on an infusion with 10% dextrose with insulin. He was subsequently found to be in urinary retention and a catheter was inserted, which drained 1700 ml. A subsequent renal function profile, 24 hours after admission, demonstrated improvement with urea 39 mmol l-1, creatinine 300 micromol/L and potassium 3.0 mEq/L.